Christopher P. Filson, MD, MS, Adam Kibel, MD, and Stacy Loeb, MD, MS, highlight the year’s most important advances in the disease state.
Noteworthy prostate cancer-related research from 2018 span a wide range, from diagnostic advances to breakthroughs in treatment of metastatic and non-metastatic disease. To recap the year in prostate cancer research, Urology Times asked Christopher P. Filson, MD, MS, Adam Kibel, MD, and Stacy Loeb, MD, MS, to highlight the year’s most important advances in the disease state.
Christopher P. Filson, MD, MS
Assistant professor of urology, Emory University School of Medicine, Atlanta
In my estimation, 2018 was a banner year for major advances in prostate cancer research, and it is hard to limit this to a few noteworthy developments. Here are three that I believe deserve attention and accolades.
SPARTAN and PROSPER trials for men with M0 castration-resistant prostate cancer. In these placebo-controlled studies, men with non-metastatic castration-resistant prostate cancer on androgen deprivation therapy were randomized to additional apalutamide (Erleada) in SPARTAN, (N Engl J Med 2018; 1408-18) or enzalutamide (XTANDI) in the PROSPER trial (N Engl J Med 2018; 378:2465-74). The studies demonstrated that use of these competitive inhibitors of the androgen receptor was associated with up to 2 years of improved metastasis-free survival, compared to placebo. These trials support the use of additional therapy for men who otherwise would have to await development of metastases before advancing to the next line of therapy.
PRECISION trial of pre-biopsy prostate magnetic resonance imaging for biopsy-naÃ¯ve men. This multicenter randomized trial assessed whether performance of multiparametric prostate MRI prior to prostate biopsy improved detection of clinically significant cancer (N Engl J Med 2018; 378:1767-77). Over one-quarter of men who underwent pre-biopsy MRI avoided a prostate biopsy. Furthermore, men who were randomized to undergo an MRI had an absolute 12% increased likelihood of being diagnosed with clinically significant cancer (ie, Gleason score 7+) and a 13% decreased likelihood of being diagnosed with insignificant cancer.
Results from this study support the use of pre-biopsy prostate MRI as standard-of-care for all biopsy-naÃ¯ve men considering prostate biopsy.
STAMPEDE trial and primary radiotherapy for men with oligometastatic prostate cancer. This randomized trial examined the role of primary radiotherapy to the prostate for men with metastatic cancer (Lancet 2018; 392:2353-66). Though overall survival did not improve for the entire cohort receiving radiotherapy, a preplanned subgroup analysis of men with low-volume metastatic burden revealed a 32% lower risk of death at 3 years (corresponding to a 3.6-month improvement in survival) versus those receiving current standard-of-care treatment. As the benefit was limited to a subgroup in this study, some controversy will persist surrounding the idea of primary radiotherapy being a standard-of-care for men with oligometastatic disease. The results from on ongoing SWOG study examining this question are eagerly anticipated.
Next:Dr. Kibel on MRI-guided diagnosis, advances in precision medicine, and moreAdam Kibel, MD
Elliott Carr Cutler Professor of Surgery, Harvard Medical School, and chief of urology at Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston
The past year has seen multiple advances in the diagnosis and treatment of prostate cancer. Notable developments include MRI-guided diagnosis, systemic treatment for metastatic prostate cancer, advances in precision medicine, and positron emission tomography imaging in prostate cancer.
MRI-guided diagnosis of prostate cancer. Data over the past year have solidified multiparametric MRI in the management of prostate cancer. In the patient wanting to avoid biopsy, an MRI is a good screen. In men undergoing a biopsy, the combination of both targeted biopsy and systematic biopsy offers the best strategy to identify clinically relevant cancer.
Systemic treatment for metastatic prostate cancer. Docetaxel (Taxotere) was introduced almost 15 years ago for the treatment of castrate-resistant prostate cancer. The improvement in life expectancy was measured in months. During the past 2 years, trials have demonstrated a survival advantage measured in years for docetaxel and abiraterone (ZYTIGA) for men with metastatic castrate-sensitive prostate cancer. In addition, trials have shown that apalutamide and enzalutamide increase metastasis-free survival in men with non-metastatic castrate-resistant disease.
Advances in precision medicine. A revolution in sequencing has revealed that genetic signatures in the tumor and in the patient’s normal DNA are associated with aggressive prostate cancer. In addition, some of these genetic changes improve the patient’s response to specific drug treatments. For example, defects in BRCA2 not only predispose the patient to aggressive disease but also improve the tumor response to PARP inhibitors. This has opened the field of precision medicine to prostate cancer patients.
PET imaging in prostate cancer. Bone and computed tomography scans have been the best imaging modalities to detect metastatic disease. They unfortunately do not adequately detect metastasis. While FDG PET has proven useful in multiple malignancies, its utility in prostate cancer is limited due to the low level of glucose metabolism. Recently, novel PET imaging using PSMA and fluciclovine (Axumin), which are radiolabeled, have become or are shortly going to become available. These have improved sensitivity to detect metastatic disease and therefore are going to profoundly alter our management as occult metastatic deposits are identified. This is the beginning of a revolution in patient care.
Next:Dr. Loeb on the USPSTF PSA recommendations, PRECISION trialStacy Loeb, MD, MS
Assistant professor of urology and population health, New York University Langone and the Manhattan VA, New York
In May 2018, the U.S. Preventive Services Task Force finalized its updated recommendations for PSA screening. For men ages 55 to 69 years, they recommend an individual decision about prostate cancer screening (Grade C). These new recommendations are in line with other professional organizations, which recommend shared decision-making about screening, and represent a significant change from the USPTF 2012 recommendations against screening for men of all ages. This is important so that men are informed about the pros and cons of screening to decide if it is right for them.
The PRECISION trial came out in 2018 showing that performing an MRI for risk stratification before initial biopsy followed by MRI-targeted biopsy was superior to the traditional pathway of standard transrectal ultrasound-guided biopsy for men with an elevated PSA. Previous guidelines recommended considering MRI before repeat prostate biopsy, and this study provides high-level evidence to show that MRI is also beneficial before the initial prostate biopsy.